NSAIDs Drug Interactions

NSAID is an acronym for non-steroidal anti-inflammatory drug. Alternate names include non-steroidal anti-inflammatory medicines (NSAIMs) or non-steroidal anti-inflammatory agents (NSAIAs). They are a large class of drugs and include common prescription and over-the-counter drugs. Aspirin, ibuprofen, naproxen, and diclofenac are all examples of NSAIDs.

Click here for a more detailed introduction: What are NSAIDs?

What are NSAIDs Used For?

As a group, NSAIDs are able to significantly reduce pain, inflammation, and fever. They are commonly used as painkillers, especially the over-the-counter varieties.

They are often used to treat headaches, colds or flu-like symptoms, and minor injuries such as sprains and strains.  Prescription NSAIDs are used for inflammatory conditions such as rheumatoid arthritis, osteoarthritis and gout.

For more about how NSAIDs are used, click here: Common Uses of NSAIDs

Side Effects of NSAIDs

Even on their own, NSAIDs can have significant side effects. These adverse effects can be worsened by the addition of other drugs, or NSAIDs’ side effects can interfere with the action of other medications.

The most common adverse reactions typically involve the digestive system: nausea, indigestion, and diarrhea. Severe effects such as bleeding or ulcers can also occur, especially in people taking high doses for extended periods of time. Likewise, extended use can increase the risk of heart attack, stroke, and the high blood pressure that can cause them.

There is more about the possible negative effects here: NSAIDs Side Effects

Possible Drug Interactions

This is far from an exhaustive list. Individual medicines may interact differently, and one person’s body may react differently from another person’s. These are some common drug mixtures that may impact your health. If you regularly take any medicine, make sure you speak to a doctor or pharmacist before taking NSAIDs.


Caffeine amplifies the effects of NSAIDs and accelerates their normal chemical action. Many people find that mixing caffeine with NSAIDs gives faster relief and better pain relief. For this reason, some drug manufacturers make pills that contain both an NSAID and caffeine. A popular example is Excedrin (a trademark of Bayer), which contains a mixture of aspirin and caffeine.

It’s important to know, however, that brand name medications tend to be more expensive. A similar effect can be had by taking an over-the-counter NSAID (aspirin, ibuprofen, or naproxen) with a cup of coffee, tea, or a caffeinated soda. Be sure that the medicine doesn’t already contain caffeine, however, as too much caffeine can be uncomfortable or dangerous to people with a heart condition.

A side effect of using NSAIDs with caffeine, however, is that some of the digestive side effects can be more intense. Caffeine already has an effect on the digestive system, so it’s more likely to develop problems like diarrhea, upset stomach, or gas with this mixture.


Alcohol should not be mixed with NSAIDs, especially prescription-strength NSAIDs. There is an increased risk of severe side effects to the stomach and intestines, especially bleeding or ulcers. And though rare, in individuals who drink heavily or have an existing liver condition, NSAIDs increase the risk of liver damage.

Some medical professionals do say that people are able to drink moderately on NSAIDs. The suggested limits are 3 to 4 drinks per day for men and 2 to 3 drinks per day for women. A drink in this case would be a can/bottle of beer, glass of wine, or a fluid ounce (shot) of liquor. This is limited to over-the-counter NSAIDs, and it still isn’t recommended to add alcohol into the mix.

Anti-Clotting Medication (Warfarin, etc)

The blood-thinning properties of NSAIDs is well known, especially aspirin, which is often prescribed in low doses as a preventative measure in people with heart disease. Though different NSAIDs have this property to different degrees, it’s present in all members of this class of drugs. When combined with an anti-clotting drugs such as warfarin (i.e. Coumadin), there is a real danger of excessive bleeding, either externally or internally. The two should never be mixed.

Blood Pressure Medications (ACE inhibitors)

Though individual drugs have varying effects, long-term use of prescription NSAIDs has been linked to increased blood pressure. Though over-the-counter versions, or occasional use, don’t tend to have a lasting effect on blood pressure, NSAIDs can interfere with the normal function of blood pressure medications, especially ACE inhibitors. There is a long list of ACE inhibitors marketed under a variety of brand names, so it’s best to ask your doctor or pharmacist if you’re unsure.


Also called “water pills,” diuretics are medicine used to increase the rate of urination. This is helpful to people with heart disease or a buildup of toxic materials in the blood that need to be eliminated. NSAIDs restrict the flow of blood to the kidneys, however, interfering with the effects of diuretics. Again, there are a variety of drugs used as diuretics and if you’re unsure if you’re taking one of them, speak to a healthcare provider.


Lithium is often used as a drug to stabilize the patient’s emotions, and it may be sold in the drug Eskalith. As lithium is removed from the body via the kidneys, and NSAIDs reduce the natural function of the kidneys, the combination can lead to a toxic buildup of lithium in the system.  The two drugs shouldn’t be mixed except under the supervision of a doctor.


Methotrexate is often used to treat cancer and autoimmune disorders by preventing the grown of clusters of new cells. It’s often used as a treatment for arthritis as well, which is where it can run into NSAIDs as they are often used to treat the symptoms of arthritis as well. Methotrexate is eliminated by the kidneys, but NSAIDs impair the function of the kidneys by reducing blood flow. The combination can lead to a potentially toxic buildup of methotrexate in the system.

Anti-Depressants (SSRIs)

There is some evidence that NSAIDs interfere with the function of SSRIs (selective serotonin re-uptake inhibitors). However, the real concern of mixing these two medications is that the combination greatly increases the risk of bleeding in the stomach and intestines. Doctors tend to recommend other pain-relief medications to people also taking SSRIs.


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